DESCRIPTION (from applicants abstract): Cyclic vomiting syndrome (CVS) is a disabling condition characterized by multiple severe and distinct episodes of nausea, vomiting, lethargy and variable other symptoms separated by asymptomatic intervals. Although CVS is generally believed to be a (predominantly) childhood variant of migraine, its etiology and pathogenesis are poorly understood. Several features of CVS, including a maternal bias in inheritance, suggest that mitochondrial DNA (mtDNA) sequence variations/mutations may be involved in its etiology. A significant subset of children with CVS have additional neuromuscular disease manifestations including cognitive dysfunction and epilepsy. Maternal inheritance of migraine and/or various neuromuscular disorders and lactic acidosis are present in ten children with CVS followed by the investigators, strongly suggesting that mtDNA mutations are involved in at least some cases. An inherited complex mtDNA rearrangement was found in one. Preliminary results using temporal temperature gradient gel electrophoresis (TTGE) found heteroplasmic sequence variations in the mtDNA D-loop in 2 additional CVS cases. TTGE is a novel mutation detection assay which was developed for use with mtDNA by the PI and collaborators. TTGE is sensitive and cost effective relative to other methods and for the first time permits the screening of large groups of patients for mutations throughout the entire mtDNA. Since mtDNA sequence variations are postulated to be more likely involved among CVS sufferers with additional neuromuscular disease manifestations, in the first sub-study 50 of these individuals will be screened by TTGE for all sequence variations throughout the mtDNA. The incidence of CVS cases caused by mtDNA sequence variations will be determined in a second sub-study in which the mtDNA in an unbiased group of 100 CVS sufferers will be screened. All sequence variations found in CVS sufferers will be compared against those found upon an identical screening of 100 control individuals, and any of interest will be sequenced. Pathogenicity of suspected mutations will be determined in rho negative cybrids. An extensive amount of clinical and laboratory data will be collected in all patients, allowing for the comparison of CVS sufferers with and without mtDNA mutations.